In persons at higher risk for colon cancer (e.g., those with sporadic adenoma or ulcerative colitis), compared to those at lower risk, colonic epithelial cell proliferation kinetics are altered. We have shown previously that calcium supplementation appears to normalize the distribution of proliferating cells without affecting the proliferation rate in the colorectal mucosa of sporadic adenoma patients. In a pilot randomized, double-blind, placebo-controlled, clinical trial conducted concurrently with our previously published sporadic adenoma trial, we tested whether calcium supplementation can also modulate cell proliferation kinetics in patients with ulcerative colitis. Ulcerative colitis patients (n = 31) were randomized to placebo or 2.0 g of supplemental calcium daily. Colorectal epithelial cell proliferation was determined by immunohistochemical detection of proliferating cell nuclear antigen labeling of cells in "nonprep" rectal biopsies taken at randomization and after 2 months treatment. All biopsies were scored by one reviewer. Differences in mean follow-up minus baseline labeling index (LI; the proportion of colon crypt epithelial cells that were labeled) and in the phi(h) (proportion of labeled cells that were in the upper 40% of the crypts) were compared with analysis of covariance. Pill-taking adherence was 97%. Biopsy-scoring reliability was high (r = 0.89). The pooled baseline LI and phi(h) were 6.3% and 5.6%, respectively. The LI in the calcium group decreased by 0.5% (proportionately, 3%) more than in the placebo group (P = 0.91). Similarly, the phi(h) in the calcium group decreased by 0.3% (proportionately, 10%) more than in the placebo group (P = 0.85). This pilot study does not suggest that 2.0 g of calcium as calcium carbonate daily can substantially normalize either the rate or distribution of proliferating cells over a 2-month period in the colon crypts of patients with ulcerative colitis; a more definitive answer to the question of whether calcium may be effective would require a study with a larger sample size and/or other study design modifications.